Tag: cancer prevention

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Statin Therapy May Prevent Cancer by Blocking Inflammatory Protein

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Lung cancer metastasis. Credit: National Cancer Institute

A new study led by investigators from Mass General Cancer Center, a founding member of the Mass General Brigham healthcare system, reveals that statins may block a particular pathway involved in the development of cancer that results from chronic inflammation. The findings are published in Nature Communications.

“Chronic inflammation is a major cause of cancer worldwide,” said senior author Shawn Demehri, MD, PhD. “We investigated the mechanism by which environmental toxins drive the initiation of cancer-prone chronic inflammation in the skin and pancreas. Furthermore, we examined safe and effective therapies to block this pathway in order to suppress chronic inflammation and its cancer aftermath.”

Demehri and his colleagues’ study relied on cell lines, animal models, human tissue samples and epidemiological data. The group’s cell-based experiments demonstrated that environmental toxins (such as exposure to allergens and chemical irritants) activate two connected signaling pathways called the TLR3/4 and TBK1-IRF3 pathways. This activation leads to the production of the interleukin-33 (IL-33) protein, which stimulates inflammation in the skin and pancreas that can contribute to the development of cancer.

When they screened a library of U.S. Food and Drug Administration–approved drugs, the researchers found that a statin, pitavastatin, effectively suppresses IL-33 expression by blocking the activation of the TBK1-IRF3 signalling pathway. In mice, pitavastatin suppressed environmentally-induced inflammation in the skin and the pancreas and prevented the development of inflammation-related pancreatic cancers.

In human pancreas tissue samples, IL-33 was over-expressed in samples from patients with chronic pancreatitis and pancreatic cancer compared with normal pancreatic tissue. Also, in analyses of electronic health records data on more than 200 million people across North America and Europe, use of pitavastatin was linked to a significantly reduced risk of chronic pancreatitis and pancreatic cancer.

The findings demonstrate that blocking IL-33 production with pitavastatin may be a safe and effective preventive strategy to suppress chronic inflammation and the subsequent development of certain cancers.

“Next, we aim to further examine the impact of statins in preventing cancer development in chronic inflammation in liver and gastrointestinal tract and to identify other novel, therapeutic approaches to suppress cancer-prone chronic inflammation” said Demehri.

Source: University of North Carolina at Chapel Hill

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Daily Vitamin D Could Reduce Cancer Mortality

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Vitamin D intake could reduce cancer mortality in the population by 12% – provided the vitamin is taken daily. This was the result of an evaluation of 14 studies of the highest quality conducted at the German Cancer Research Center with a total of almost 105 000 participants.

Vitamin D deficiency is widespread worldwide and is particularly common among cancer patients. Averaged over the year, the vitamin D blood levels of about 15% of German adults are below the threshold for a pronounced vitamin D deficiency*. In contrast, in a study of colorectal cancer patients, researchers diagnosed vitamin D3 deficiency in 59% of participants, which was also associated with unfavourable prognosis.

Potential effects of vitamin D supplementation and the development or prognosis of cancer have already been investigated in numerous studies. “Based on current studies, vitamin D3 supplementation probably does not protect against developing cancer, but it could reduce the likelihood of dying from cancer. However, previous studies on cancer mortality have yielded very different results, and we were interested in the reasons for this,” said Ben Schöttker, an epidemiologist at the German Cancer Research Center. “By re-evaluating all previous studies on the topic, we wanted to help produce robust results on this issue, which is so relevant to population health.

To investigate the effectiveness of vitamin D3 on cancer mortality in the population and on the survival of cancer patients, Ben Schöttker and colleagues conducted a systematic literature search that identified 14 studies with a total of nearly 105 000 participants. The researchers considered only studies of the highest quality whose participants had been randomly assigned to the vitamin D3 arm or the placebo arm.

When all 14 studies were pooled, no statistically significant results emerged. However, when the studies were divided according to whether vitamin D3 was taken daily in a low dose** or in higher doses administered at longer intervals**, a large difference was seen. In the four studies with the infrequent higher doses, there was no effect on cancer mortality. In contrast, in the summary of the ten studies with daily dosing, the researchers determined a statistically significant twelve percent reduction in cancer mortality.

“We observed this twelve percent reduction in cancer mortality after untargeted vitamin D3 administration to individuals with and without vitamin D deficiency. We can therefore assume that the effect is significantly higher for those people who are actually vitamin D deficient,” says Ben Schöttker. He explains the better efficacy of daily doses of vitamin D3 by the more regular bioavailability of the active agent, the hormone 1,25-dihydroxyvitamin D, which is only produced by reactions of vitamin D in the body and can presumably inhibit tumor growth.

A more detailed analysis of the studies with daily intake further revealed that people aged 70 and older benefited most from vitamin D3 therapy. In addition, the effect was most evident when vitamin D intake was started before the cancer diagnosis.

Hermann Brenner, epidemiologist and prevention expert at DKFZ, adds: “This work underlines the great potential of vitamin D3 administration in the prevention of cancer deaths. Regular intake at low doses** is associated with almost negligible risk and very low cost.”

* The threshold blood 25-hydroxyvitamin D level used for vitamin D deficiency was 30 nmol/L (= 12 ng/ml). If individuals with less severe vitamin D deficiency (blood 25-hydroxyvitamin D level < 50 nmol/L (= 20 ng/mL)) are added, slightly more than half of Germans have at least one deficiency. However, there are also guidelines that use other thresholds. Since the vitamin D level in the blood depends primarily on the tanning of the skin, this percentage also varies greatly with the seasons.

** In the studies, daily low doses were 400 to 4000 IU per day, and higher-doses administered at longer intervals were 60 000 to 120 000 IU once per month or less.

Source: German Cancer Research Center